Summary: When combined with psychological and emotional support, a new study shows that one dose of psilocybin can help reduce depression and symptoms associated with major depressive disorder (MDD).
Key Points:
- The use of ketamine, esketamine, and other medications with dissociative/psychedelic properties has increased in recent years.
- Psilocybin is a psychedelic medication currently in human clinical trials to treat major depressive disorder (MDD).
- These new medications are known for their ability to reduce depressive symptoms more quickly than traditional antidepressants.
- Initial research into the safety and effectiveness of psilocybin is promising.
A New Generation of Medication for Depression
According to the World Health Organization (WHO), depression is the second most common mental health disorder in the world, affecting approximately 332 million people, while anxiety is the most common mental health disorder in the world, affecting approximately 359 million people. That’s roughly four percent of the adult population with depression, and roughly four and a half percent of the population with anxiety.
In this article, we’ll focus on a new treatment for major depressive disorder (MDD) called psilocybin. We’ll use data from a new study called “Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial.” The research team behind this study designed a random-controlled trial – meaning one group gets the medication and another gets a placebo – to answer the following question:
Is psilocybin safe and effective in patients with major depressive disorder?
Before we share the details of the study, we’ll take a quick look at the latest data on rates of major depressive disorder and antidepressant use in the U.S. as reported in a publication from the Centers for Disease Control (CDC) called “New Reports Highlight Depression Prevalence and Medication Use in the U.S.”
Here’s the data:
Prevalence of Depression and Medication for Depression: 2023
Diagnosis of depression:
- Total: 13.1%
- By age group:
- 12-19: 19.2%
- 20-39: 16.6%
- 40-59: 10.8%
- 60+: 8.7%
Use of prescription medication for depression:
- Total: 11.4%
- By age group:
- 18-44: 10.7%
- 45-64: 12.1%
- 65-74: 12.4%
- 75+: 11.3%
Evidence shows that around 30 percent of people with major depressive disorder (MDD) don’t experience a satisfactory treatment response with standard antidepressant medication. That’s why there’s significant interest in finding new medications for depression that work for more people, and why there’s significant interest in the possibility that one dose of psilocybin may help reduce depression and depressive symptoms in people with major depressive disorder (MDD).
Let’s take a look at that new study, and learn what the researchers found.
One Dose of Psilocybin to Reduce Depression: Does It Work – And is It Safe?
To conduct the experiment, researchers recruited a total of 104 adults aged 21 to 65 years who met criteria established by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) for current diagnosis of a minimum 60-day episode of major depressive disorder (MDD).
All adults were considered medically healthy. Researchers divided participants into two groups, with half in the psilocybin group and half in the placebo group. After a month-long screening period that included a taper off any other antidepressants, each participant completed baseline assessments with the two following standardized mental health assessments:
- The Montgomery-Asberg Depression Rating Scale (MADRS)
- The Sheehan Disability Scale (SDS)
After an orientation, each participant received either:
- 25 mg oral psilocybin (psilocybin group)
- 100 mg niacin, or vitamin B3 (placebo group)
All participants received psychological support during the dosing session and throughout the study period from trial clinicians but discontinued formal psychotherapy during the orientation and throughout the duration of the study.
After the dosing day, all participants completed follow up MADRS assessments after 2 days, 8 days, 15 days, 29 days, and 43 days. In addition, all participants completed follow up SDS assessments after 2 days, 8 days, 29 days, and 43 days. Researchers established their primary outcome measures as changes in MADRS at day 8, and changes in SDS at day 43.
Here’s what they found.
Outcomes: Psilocybin vs. Placebo for Depression: MADRS Scale
First follow up, Day 2:
- Psilocybin: 2.7 point reduction
- Placebo: 2.7 point reduction
Second follow up, Day 8:
- Psilocybin: 17.8 point reduction
- Placebo: 5.8 point reduction
Third follow up, Day 15:
- Psilocybin: 18.0 point reduction
- Placebo: 6.9 point reduction
Fourth follow up, Day 29:
- Psilocybin: 19.2 point reduction
- Placebo: 5.5 point reduction
Final follow up, Day 43:
- Psilocybin: 19.1 point reduction
- Placebo: 6.8 point reduction
In this data set, we see a significant reduction in MADRS scores for participants who received psilocybin compared to participants who received placebo – a reduction three times greater for psilocybin compared to placebo.
Outcomes: Psilocybin vs. Placebo for Depression: Sheehan Disability Scale
First follow up, Day 8:
- Psilocybin: 3.85 point reduction
- Placebo: 1.49 point reduction
Second follow up, Day 15:
- Psilocybin: 3.97 point reduction
- Placebo: 1.76 point reduction
Third follow up, Day 29:
- Psilocybin: 4.26 point reduction
- Placebo: 1.7 point reduction
Final follow up, Day 43:
- Psilocybin: 4.07 point reduction
- Placebo: 1.76 point reduction
In this data set, we see a significant reduction in scores on the SDS, with a reduction twice as large for participants who received psilocybin compared to participants who received placebo. With regards to safety and adverse events associated with psilocybin, the research team reports:
“Psilocybin was generally well-tolerated, with most AEs being of mild or moderate severity and generally limited to the acute dosing period.”
We’ll discuss this data below.
Psilocybin and Depression: Safe and Effective in Clinical Conditions With Expert Support
The short-term impact of the new generation of depression medication, including those with dissociative effects such as ketamine and esketamine, and those with psychedelic effects such as psilocybin, is well-known and well-established. In most cases, patients report fast-acting symptom relief from depression – some immediately, and some beginning within 24 hours. However, important treatment factors that are not yet well established include:
- Duration of symptom relief: there’s significant variation reported in studies.
- Contribution of psychotherapy to symptom relief: not all studies require discontinuation of psychotherapy during testing periods.
In other words, researchers and clinicians have not yet fully determined how long the benefit of these medications last or whether simultaneous/concurrent psychotherapy explains part of the symptom relief. This study offers preliminary data on both of those outstanding questions: the duration of symptom relief for one dose of psilocybin is at least 43 days, and that relief occurred without simultaneous/concurrent psychotherapy.
Here’s how the research team describe their results:
“Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin – when administered with psychological support – may hold promise as a novel intervention for MDD.”
That’s good news for patients and providers: this may be a new and effective pharmaceutical approach for all patients with depression. We’re particularly interested in the next step, and are eager to learn whether combining a new medication like psilocybin with standard psychotherapy and lifestyle support can yield even greater symptom reduction than psilocybin administered with basic psychological and emotional support.
We’ll keep an eye on the research, and report what we learn here, as soon as new information becomes available.
Gianna Melendez
Jodie Dahl, CpHT